Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using THALIDOMIDE
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Gastrointestinal |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/16/2013 |
| Start Date: | May 2006 |
| End Date: | October 2010 |
| Contact: | Paula Freeman-Vida, B.S. R.N |
| Email: | Freemanvidap@ccf.org |
| Phone: | 216.445.1770 |
Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using Thalidomide
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms
include the development of ascites, hepatic encephalopathy, or variceal bleeding. The
development of portal hypertension represents a critical transition point in the natural
history of cirrhosis, contributing to, or directly responsible for all of these events. It
is defined by an increase in intrahepatic vascular resistance to portal venous inflow, with
the subsequent development of collateral vessels, such as esophageal or gastric varices. As
portal pressures rise over time, however, the resulting increase in variceal size and wall
tension translates into an increasing likelihood of rupture and bleeding, leading to death
in about 30% of patients. Over the last twenty years, data have emerged regarding the role
of tumor necrosis factor (TNFα) in portal hypertension from animal models as well as in
vitro experiments. Portal hypertension is a condition characterized by vasodilatation and a
hyperdynamic circulation, driven by relative overproduction of nitric oxide23. In animal
trials using inhibitors of TNF it has been shown to decrease the development of the
hyperdynamic circulatory state and portal pressure.24-25 Based on these data, investigators
have examined the role of TNF inhibition with thalidomide. Significant improvement in
blocking the development of the hyperdynamic circulation and portal pressures was
demonstrated.26 Human trials have also show the efficacy of thalidomide in reducing portal
pressures. In that these trials have shown promising results further investigation is
Treatment duration with thalidomide will be for 16 weeks, beginning in the hospital setting
immediately after the index bleed, and clinical follow-up additional six months. Follow-up
in both the hepatology, outpatient clinic area and the endoscopy suite will occur. Step
wise thalidomide dosing will be 100 mg/d once a day at night. If no evidence of toxicity is
noted after 5 doses, the dose will be increased to 200 mg/d, and continued on that dose as
an outpatient until completion of the study protocol at 16 weeks. Patients will be followed
daily while inpatients, and subsequently at two-week intervals upon discharge. Females of
child-bearing potential will be seen weekly for the first month and must have a confirmed
negative pregnancy test prior to being dispensed the next one week supply of study drug.
After the first month, females of child-bearing potential will be seen every two weeks as
will all other subjects. Standard follow-up medical care after esophageal variceal bleeding
in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either
endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta
blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of
interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status
Patients will initially be followed daily while hospitalized. outpatient visits will occur
every two-week intervals upon discharge. Standard follow-up medical care after esophageal
variceal bleeding in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either
endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta
blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of
interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status the
need for TIPS, liver transplantation or death. In addition, patients and their families will
be questioned for any evidence of potential toxicity as assessed by using the CTC Toxicity
grade version 3, or adverse outcomes by one of the study investigators as well as a nurse
coordinator, using a standardized questionnaire along with a regular clinical
Inclusion Criteria:
- Endoscopic confirmation or portal hypertension related GI bleeding
- Over the age of 18 with the ability to willingly sign an informed consent
- Adequate performance status and cognitive ability
- Patients must be willing to comply with all FDA-mandated prescribing and safety while
taking Thalidomide
- Hemodynamically stable with no evidence of ongoing bleeding (defined as a Hgb that
has not varied by more than 10% over 12 hour period.)
Exclusion Criteria:
- No other serious illness or medical condition including unstable cardiac disease
requiring treatment, new onset crescendo or rest angina. Stable exertional angina is
acceptable.
- No history of significant neurological or psychiatric disorders including psychotic
disorders, dementia, or seizures or active infection
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